血红素加氧酶-1参与博莱霉素致大鼠肺纤维化机制

Mechanisms of heme oxygenase-1 in the pathogenesis of Bleomycin induced pulmonary fibrosis in rat

目的观察血红素加氧酶-1(HO-1)对博莱霉素(BLM)致大鼠肺纤维化模型病理生理改变的影响,探讨HO-1参与BLM致大鼠肺纤维化发病机制。方法通过BLM复制大鼠肺纤维化模型,同时设立生理盐水(NS)组和HO-1抑制剂锌原卟啉(Znpp)组。检测支气管肺泡灌洗液(BALF)中细胞计数及中性粒细胞百分比、转化生长因子-β(TGF-β)和总胆红素含量;检测肺组织中还原型谷胱甘肽(GSH)和羟脯氨酸(HYP)含量。结果HO-1水平被抑制后,不能改善炎症细胞浸润肺组织,但可以有效抑制TGF-β、总胆红素和HYP水平,减少GSH耗竭。结论HO-1通过其氧化损伤和促纤维化机制促进BLM致大鼠肺纤维,但不参予早期炎症反应。

[Objective] To study the effect of heine oxygenase-1 （HO-1） on patho-physiological changes of Bleomycin （BLM） induced pulmonary fibrosis in rat, and to investigate the mechanisms of HO-1 in the pathogenesis of pulmonary fibrosis. [Methods] The pulmonary fibrosis model in rat was established by Bleomycin. Healthy SD rats （n=60） were randomly divided into normal sodium （NS） group, BLM group and inhibitor of heme oxygenase-1- zinc protoporphyrin （Znpp） group. The cell counting and neutrophil percentage, the level of total bilirubin and transforming growth factor-β （TGF-β） in the bronchoalveolar lavage fluid （BALF） and the content of reduced glutathione （GSH） and hydroxyproline （HYP） in the lung tissue were tested. [Results] After the level of HO-1 had been inhibited, the attenuation of inflammatory cell infdtration in lung tissue was not happened ,but the level of TGF-β, total bilirubin, HYP and the exhaustion of GSH was inhibited evidently. [Conclusion] The mechanisms of HO-1 in the pathogenesis of BLM induced pulmonary fibrosis in rat are those it can oxidize, damage and fiberize, but not inflame the lung issue.